Since the capillary endothelial ability to regulate its volume should be prerequisite for maintaining the function of the barrier, we investigated the response of intrinsic endothelial mechanisms to hypotonicity. The exposure of viable endothelium to a medium of half normal osmolality resulted in immediate cellular swelling, reduction in transmembraneous potential and intracellular pH but without evidence of permeability changes to trypan blue bound proteins. A rapid recovery with complete normalization of cell volume and membrane potential but with limited restoration of intracellular pH took place within 30 - 60 minutes although the osmolality of the medium remained low. These results strongly suggest that the cerebrovascular endothelium has a build-in high capacity for self-regulation which undoubtfully is important for normal function of BBB.